Browse

Phase II trial of dacomitinib in patients with HER2-positive gastric cancer

Cited 21 time in Web of Science Cited 20 time in Scopus
Authors
Oh, Do-Youn; Lee, Kewn-Wook; Cho, Jae Yong; Kang, Won Ki; Im, Seock-Ah; Kim, Jin Won; Bang, Yung-Jue
Issue Date
2016-10
Citation
Gastric Cancer, Vol.19 No.4, pp.1095-1103
Keywords
HER2Gastric cancerDacomitinibHER2 ECDSoluble E-cadherin
Abstract
Dacomitinib, an irreversible panHER inhibitor, shows significant preclinical antitumor activity in human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC). The aim of this study was to evaluate the clinical activity of dacomitinib and discover potential biomarkers in HER2-positive GC patients. We enrolled previously treated advanced HER2-positive GC [HER2 FISH (+) or HER2 IHC 3+] patients. The patients received dacomitinib 45 mg once daily. A total of 27 patients were enrolled. The number of prior chemotherapy regimens was 1 in 7 patients (26 %), 2 in 9 patients (33 %), and more than 2 in 11 patients (41 %). Seven patients had received prior anti-HER2 therapy. The 4-month progression-free survival (PFS) rate was 22.2 % and median PFS was 2.1 months (95 % CI, 2.3-3.4) There were 2 partial response (PRs) and 9 stable disease (SDs), resulting in 7.4 % (95 % CI, 0-17.5 %) of response rate (RR) and 40.7 % (95 % CI, 21.9-59.6 %) of disease control rate (DCR). Eleven patients (41 %) showed some degree of tumor shrinkage. Overall survival was 7.1 months (95 % CI, 4.4-9.8). The most common toxicities were skin rash, diarrhea, and fatigue, most of which were grade 1 or 2. The C-trough of dacomitinib was lower in gastrectomy patients than nongastrectomy patients. Higher serum levels of HER2 extracellular domain (ECD) and lower levels of soluble E-cadherin (sECAD) correlated with higher dacomitinib activity. Dacomitinib functions as a single agent in HER2-positive GC patients with a tolerable safety profile. HER2 ECD and sECAD have the potential to be biomarkers for patient selection in a panHER inhibition strategy for HER2-positive GC. (ClinicalTrials.gov: NCT01152853).
ISSN
1436-3291
URI
https://hdl.handle.net/10371/173090
DOI
https://doi.org/10.1007/s10120-015-0567-z
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse